Technological improvements in biochemical mass spectrometry have changed the way biomolecules are examined. No longer are scientists relying solely on gels or other methods that have a high degree of error and a low degree of specificity. Yet even given the broad success of techniques such as electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) there is still significant potential for improvement to address biochemical problems. A new and promising strategy for mass spectrometry, laser desorption/ionization from a porous silicon surface, is a marriage between micromaterial fabrication and microchemical approaches combined with laser-based desorption ionization techniques. Desorption/ionization on silicon (DIOS) uses porous silicon to trap analytes deposited on the surface and UV laser radiation is absorbed by the silicon surface facilitating vaporization and ionization. Preliminary experiments with DIOS-MS on biomolecules have allowed for the generation of intact molecular ions with little or no fragmentation and sensitivity at least as high as MALDI-MS. The primary goal of the proposed research is to optimize porous silicon preparation for a large variety of biomolecules, high throughput applications, and ultimately for the large-scale manufacture of these surfaces. Given the tremendous growth in mass spectrometry-based applications for biomolecule analysis, new technology that could further improve on small molecule analysis and compatibility with microfluidics and silicon microchip technology as well as impurity tolerance, sensitivity, and automation will have an enormous impact in the biological sciences. PROPOSED COMMERCIAL APPLICATION: Given the tremendous growth in mass spectrometry-based applications for biomolecule analysis, new technology, such as desorption ionization on silicon (DIOS), that further improves mass spectrometry's compatibility with microfluidics and silicon microchip technology as well as in impurity tolerance, sensitivity, and automation will have an enormous impact in the pharmaceutical industry and biological sciences.